Neurophysiological features of STN LFP underlying sleep fragmentation in Parkinson's disease.

BACKGROUND: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear. METHOD: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication. The STN LFP features that characterised different sleep stages, correlated with arousal and sleep fragmentation index, and preceded stage transitions during N2 and REM sleep were analysed. RESULTS: Both beta and low gamma oscillations in non-rapid eye movement (NREM) sleep increased with the severity of sleep disturbance (arousal index (ArI)-betaNREM: r=0.9, p=0.0001, sleep fragmentation index (SFI)-betaNREM: r=0.6, p=0.0301; SFI-gammaNREM: r=0.6, p=0.0324). We next examined the low-to-high power ratio (LHPR), which was the power ratio of theta oscillations to beta and low gamma oscillations, and found it to be an indicator of sleep fragmentation (ArI-LHPRNREM: r=-0.8, p=0.0053; ArI-LHPRREM: r=-0.6, p=0.0373; SFI-LHPRNREM: r=-0.7, p=0.0204; SFI-LHPRREM: r=-0.6, p=0.0428). In addition, long beta bursts (>0.25 s) during NREM stage 2 were found preceding the completion of transition to stages with more cortical activities (towards Wake/N1/REM compared with towards N3 (p<0.01)) and negatively correlated with STN spindles, which were detected in STN LFPs with peak frequency distinguishable from long beta bursts (STN spindle: 11.5 Hz, STN long beta bursts: 23.8 Hz), in occupation during NREM sleep (ß=-0.24, p<0.001). CONCLUSION: Features of STN LFPs help explain neurophysiological mechanisms underlying sleep fragmentations in PD, which can inform new intervention for sleep dysfunction. TRIAL REGISTRATION NUMBER: NCT02937727.

Deceleration and acceleration capacities of heart rate in patients with drug-resistant epilepsy.

OBJECTIVE: Epilepsy and seizures can have dramatic effects on cardiac function. The aim of the present study was to investigate deceleration capacity, acceleration capacity and their 24-h fluctuations of heart rate variability in patients with drug-resistant epilepsy. METHODS: Deceleration capacity, acceleration capacity of heart rate and their 24-h dynamics derived from the phase rectified signal averaging method as well as traditional measures were analyzed in 39 patients with drug-resistant epilepsy and 33 healthy control subjects using 24-h electrocardiogram recordings. The discriminatory power of heart rate variability measures were validated by assessment of the area under the receiver operating characteristic curve. Net reclassification improvement and integrated discrimination improvement models were also estimated. RESULTS: Both deceleration capacity and absolute values of acceleration capacity were significantly lower in patients with drug-resistant epilepsy. The abnormal suppression of absolute deceleration capacity and acceleration capacity values were observed throughout the 24-h recording time (peaked at about 3 to 5 A.M.). Deceleration capacity had the greatest discriminatory power to differentiate the patients from the healthy controls. Moreover, in both net reclassification improvement and integrated discrimination improvement models, the combination of acceleration capacity or deceleration capacity with traditional heart rate variability measures has greater discriminatory power than any of the single heart rate variability features. INTERPRETATION: Drug-resistant epilepsy was associated with a significant inhibition of vagal modulation of heart rate, which was more pronounced during the night than during the day. These findings indicate that phase rectified signal averaging method may serve as a complementary approach for characterizing and understanding the neuro-pathophysiology in epilepsy, and may provide a new clue to sudden unexpected death in epilepsy.

Chronic vagus nerve stimulation reverses heart rhythm complexity in patients with drug-resistant epilepsy: An assessment with multiscale entropy analysis.

OBJECTIVE: Vagus nerve stimulation (VNS) is an adjunctive treatment in drug-resistant epilepsy. The alterations in heart rate dynamics through VNS are not well understood. This study aimed to determine changes in heart rhythm complexity in association with VNS and to relate the findings to the outcome of VNS treatment in patients with drug-resistant epilepsy. METHODS: We prospectively analyzed 32 patients with drug-resistant epilepsy, who underwent VNS implantation, and 32 age- and sex-matched healthy control subjects. The interictal heartbeat intervals were analyzed using the heart rhythm complexity with multiscale entropy (MSE) and traditional heart rate variability (HRV) analyses based on ambulatory 24-hour electrocardiograms (ECGs). RESULTS: Patients had significantly decreased complexity indices (Slope 5, Area 1-5, Area 6-15, Area 6-20) on MSE analysis and decreased HRV measurements (standard deviation of the heartbeat interval (SDNN), square root of the mean of sum of squares of the differences between adjacent RR intervals (RMSSD), pNN50, very low frequency (VLF), low frequency (LF), high frequency (HF), total power (TP)) in time and frequency domain analyses. After one year of VNS treatment in patients with drug-resistant epilepsy, there was a trend in an elevated MSE profile with significant higher values between the scales 1 and 9. Vagus nerve stimulation induces a more significant increase of MSE in VNS responders than those in the nonresponders. The conventional HRV measurements did not change. CONCLUSION: Our results suggest that heart rhythm complexity is impaired in patients with drug-resistant epilepsy, and this is at least partially reversed by VNS treatment. Furthermore, VNS-induced effects on heart rate complexity may be associated with the therapeutic response to VNS in patients with drug-resistant epilepsy.

[Interpretation of the International Standard 2017 Version of Implantable Neurostimulators].

ISO 14708-3 "Implants for surgery-active implantable medical devices-Part 3:implantable neurostimulators" 2017 version and 2008 version are compared, and changes in the standard are interpreted combined with the characteristics of the neurostimulator. The new version of the standard for the first time in the introduction mentioned a new type of non-electrode or extension's neurostimulator. Key issues that have significant impact on safety concerns such as wireless charging temperature rise, MRI acceptance criteria, etc., are given for the first time in the new version. New requirements to the wireless communication section are added, and the electromagnetic compatibility part is greatly adjusted. With more miniature non-electrode or extension's neurostimulator entering the market, standards such as electromagnetic compatibility and MRI, there will be greater adjustments.

Heart-rate variability indices as predictors of the response to vagus nerve stimulation in patients with drug-resistant epilepsy.

OBJECTIVE: To assess heart-rate variability (HRV) measures of interictal electrocardiography (ECG) for drug-resistant epilepsy and to relate the findings to the outcome of vagus nerve stimulation (VNS) treatment. METHODS: Time-domain, frequency-domain, and nonlinear analyses were used to analyze preoperative HRV measures in 32 patients with drug-resistant epilepsy who had received VNS implants at the same hospital and 32 healthy age- and sex-matched control subjects. HRV measurements based on ambulatory 24 h ECG recordings were analyzed to identify seizure reduction 1 year after VNS treatment. Responders were defined as having at least 50% seizure reduction 1 year after treatment. RESULTS: Patients with drug-resistant epilepsy had significantly lower time domain (SDNN, RMSSD, pNN50), frequency domain (VLF, LF, HF, TP), and nonlinear (SD1, SD2) HRV measurements than matched healthy controls. None of the analyzed HRV measures of the responders differed significantly from their controls, whereas those of the nonresponders had significantly lower RMSSD, pNN50, HF, and SD1 than the responders. SIGNIFICANCE: The preoperative HRV indices demonstrate that nonresponders have more pronounced impairment of their cardiac autonomic function than the responders. Presurgical HRV measurements representing parasympathetic cardiac control or vagal tone were significantly associated with the responsiveness to VNS. Thus the measurements show promise for predicting the reduction of seizure frequency after VNS treatment.

The ability of anterior thalamic signals to predict seizures in temporal lobe epilepsy in kainate-treated rats.

OBJECTIVE: To analyze the local field potential (LFP) of the anterior nucleus of the thalamus (ANT) of epileptic rats using the Generic Osorio-Frei algorithm (GOFA), and to determine the ability of the ANT LFP to predict clinical seizures in temporal lobe epilepsy. METHODS: GOFA is an advanced real-time technique used to detect and predict seizures. In this article, GOFA was utilized to process the electrical signals of ANT and the motor cortex recorded in 12 rat models of temporal lobe epilepsy (TLE) induced via the injection of kainic acid into the unilateral hippocampus. The electroencephalography (EEG) data included (1) 161 clinical seizures (each contained a 10-min segment) involving the ANT and cortical regions and (2) one hundred three 10-min segments of randomly selected interictal (no seizure) data. RESULTS: Minimal false-positives (0.51 ± 0.36/h) and no false-negatives were detected based on the ANT LFP data processed using GOFA. In ANT LFP, the delay from electrographic onset (EO) to automated onset (AO) was 1.24 ± 0.47 s, and the delay from AO to clinical onset (CO) was 7.73 ± 3.23 s. The AO time occurred significantly earlier in the ANT than in the cortex (p = 0.001). In 75.2% of the clinical onsets predicted by ANT LFP, it was 1.37 ± 0.82 s ahead of the prediction of cortical potentials (CPs), and the remainder were 0.84 ± 0.31 s slower than the prediction of CPs. SIGNIFICANCE: ANT LFP appears to be an optimal option for the prediction of seizures in temporal lobe epilepsy. It was possible to upgrade the responsive neurostimulation system to emit electrical stimulation in response to the prediction of epileptic seizures based on the changes in the ANT LFP.

Patient perspectives on the efficacy of a new kind of rechargeable deep brain stimulators(1).

PURPOSE/AIM OF THE STUDY: Rechargeable deep brain stimulation (DBS) system with longer battery life has become available for treating movement disorders. However, little information exists about the safety and management after implantation. Therefore, there is an urgent need to evaluate the recharging performance through long-term observations. MATERIALS AND METHODS: Fifty-three Parkinson's disease (PD) patients were implanted with a new rechargeable device (G102R, PINS Medical). They were observed at the baseline and 3 months, 6 months and 12 months after surgery, with measurement of the acceptance, frequency, recharging time and feeling during recharging. RESULTS: The patients with the ages between 34 and 70 (57.64 ± 7.34) years thought the system was very easy to recharge. The favorite time interval for recharging was 1 week, and 10 days and half a month also chosen. Most of the patients spent around 1 hour recharging, with no unacceptable hot feelings reported. CONCLUSIONS: The PD patients could easily and safely recharge this new rechargeable implantable neurostimulators. Thus, these neurostimulators might be an excellent choice for PD patients.

[High-risk Active Implantable Medical Devices Standards].

Objective: Comprehensive standards of active implantable medical devices with high risks are required by China's current industrial development, and standard problems and ideas are discussed in this paper. Methods: Analysis of the status of China's active implantable medical device standards and international standards. For the booming field for active implantable medical devices with high risks, international standard's problems, ideas and trends are analyzed. Results: Bottleneck of the development of China's active implantable medical device standards is the lack of Chinese medical devices industry actual independent research and development capability. China's independent standard research on the basis of independent core technology of active implantable medical devices is the opportunity to promote the internationalization of China standard. Conclusion: Improving the standards of active implantable medical devices based on independent core technology, combined with problems of existing international standards, to further improve and develop international standards and lead high level international technical standards.

Biocompatibility and magnetic resonance imaging characteristics of carbon nanotube yarn neural electrodes in a rat model.

BACKGROUND: Implantation of deep brain stimulation (DBS) electrodes is a landmark therapy for movement disorders and some mental conditions. Compared to conventional platinum-iridium (Pt-Ir) electrodes, carbon nanotube yarns (CNTY) electrodes have improved stability and interface characteristics with less distortion during high field strength MRI. Sprague-Dawley rat models were used to examine thein vivo histological and imaging properties of biocompatible CNTY throughout the subacute period. METHODS: Sprague-Dawley rats received CNTY (n = 16) or Pt-Ir control (n = 16) electrodes. Behavioral markers, body weight, and survival were recorded. Comparative histology (HE, NeuN, CD68, and GFAP) was performed at 1, 6, and 12 weeks post-implantation; 3.0T MRI was performed at 1 and 12 weeks. RESULTS: Of 32 rats, 30 (15 per group) survived implantation without reduced activity, paralysis, or incapacity to feed. Following implantation, progressive decreases in macrophage activation and neuron-depleted margins surrounding electrodes were observed in both groups. Inflammatory marker expression (CD68) was significantly lower in rats with implanted CNTY electrodes compared to controls at all time points. CNTY electrodes also caused less inflammation and shallower depths of macrophage penetration and neural disruption relative to the interface. Artifacts and distortion were observed on MRI of Pt-Ir but not CNTY electrodes. CONCLUSIONS: CNTY electrodes exhibited reduced inflammatory margins compared to Pt-Ir electrodes throughout the subacute period, indicating reduced initial trauma, better overall biocompatibility, and reduced fibrous tissue formation. Coupled with less MRI distortion, CNTY electrodes may be useful alternatives when there is a need to monitor electrode placement by MRI.

An experimental study of deep brain stimulation lead fracture: possible fatigue mechanisms and prevention approach.

OBJECTIVES: Lead fracture is a common and troublesome hardware-related complication in deep brain stimulation therapy. Frequent cervical movements are suspected as the main cause, but the underlying mechanisms are still unclear. We propose the integrity of the helical structure of the lead wires is important and conduct systematic experiments to demonstrate this. We aim to provide a new view on how lead fracture takes place. MATERIALS AND METHODS: Flexural fatigue tests were conducted on intact and stretched lead wires with a custom-made testing machine. Number of cycles until failure was recorded as the fatigue life, and the fracture morphology was observed under optical and scanning electron microscopes. RESULTS: The fatigue life of the lead wires showed dramatic decline with the severity of deformation, from 434,112 ± 10,277 cycles for an intact specimen down to 19,435 ± 2,622 cycles for a specimen elongated by approximately 20%. The morphology of the fractures revealed characteristic beach marks and striations indicating a fatigue failure. CONCLUSION: We demonstrate that integrity of the helical structure of the wires is crucial to the fatigue performance of the lead. Although the results cannot be directly extrapolated to human subjects, they suggest a possible lead fracture mechanism. The implanted lead may undergo deformation due to large-amplitude motions (e.g., falls) and develop fracture due to the deterioration in fatigue resistance, especially when it is placed at or migrates to the neck. It may be possible to effectively protect the lead by using certain surgical techniques during implantation, such as placing the connector on the calvaria or in a drilled trough at the retroauricular region with reliable fixation.

[Batteries Used in Active Implantable Medical Devices].

In recent years active implantable medical devices(AIMD) are being developed rapidly. Many battery systems have been developed for different AIMD applications. These batteries have the same requirements which include high safety, reliability, energy density and long service life, discharge indication. History, present and future of batteries used in AIMD are introduced in the article.

In vivo experimental study of thermal problems for rechargeable neurostimulators.

OBJECTIVES: Eddy currents in the metal shell and copper losses in the coils generate heat in rechargeable neurostimulators, which increases the temperature of the adjacent tissue, potentially causing thermal damage of implant patients. Hence, there is an urgent need for a simple self-help method to measure the temperature of such subcutaneous devices. MATERIALS AND METHODS: A wireless rechargeable implant system was fabricated and tested with in vivo experiments in swine to measure the increasing temperatures of both the implant device and the adjacent skin. A total of three swine were used in the study with 13 wireless charging tests. RESULTS: It was found that the temperatures of both the implant and the skin rose consistently with an approximately linear relationship in most of the charging time, demonstrating that the neurosimulator temperature could be estimated from the skin temperature. The equilibrium temperature differences are all less than 2°C. CONCLUSIONS: A convenient method was then given to monitor the adjacent skin temperature to evaluate the thermal hazards with a skin temperature threshold of 41°C. The proposed approach can be easily implemented by an implant patient at home to reduce the thermal risk, ease patient anxiety, and improve clinical outcomes.

Alteration of Excitation/Inhibition Imbalance in the Hippocampus and Amygdala of Drug-Resistant Epilepsy Patients Treated with Acute Vagus Nerve Stimulation.

An imbalance between excitation (E) and inhibition (I) in the brain has been identified as a key pathophysiology of epilepsy over the years. The hippocampus and amygdala in the limbic system play a crucial role in the initiation and conduction of epileptic seizures and are often referred to as the transfer station and amplifier of seizure activities. Existing animal and imaging studies reveal that the hippocampus and amygdala, which are significant parts of the vagal afferent network, can be modulated in order to generate an antiepileptic effect. Using stereo-electroencephalography (SEEG) data, we examined the E/I imbalance in the hippocampus and amygdala of ten drug-resistant epilepsy children treated with acute vagus nerve stimulation (VNS) by estimating the 1/f power slope of hippocampal and amygdala signals in the range of 1-80 Hz. While the change in the 1/f power slope from VNS-BASE varied between different stimulation amplitudes and brain regions, it was more prominent in the hippocampal region. In the hippocampal region, we found a flatter 1/f power slope during VNS-ON in patients with good responsiveness to VNS under the optimal stimulation amplitude, indicating that the E/I imbalance in the region was improved. There was no obvious change in 1/f power slope for VNS poor responders. For VNS non-responders, the 1/f power slope slightly increased when the stimulation was applied. Overall, this study implies that the regulation of E/I imbalance in the epileptic brain, especially in the hippocampal region, may be an acute intracranial effect of VNS.

Safety and precision of frontal trajectory of lateral habenula deep brain stimulation surgery in treatment-resistant depression.

Introduction: The lateral habenula (LHb) is a promising deep brain stimulation (DBS) target for treatment-resistant depression (TRD). However, the optimal surgical trajectory and its safety of LHb DBS are lacking. Methods: We reported surgical trajectories for the LHb in six TRD patients treated with DBS at the General Hospital of the Chinese People's Liberation Army between April 2021 and May 2022. Pre-operative fusions of magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to design the implantation trajectory of DBS electrodes. Fusions of MRI and CT were conducted to assess the safety or precision of LHb DBS surgery or implantable electrodes locations. Results: Results showed that the optimal entry point was the posterior middle frontal gyrus. The target coordinates (electrode tips) were 3.25 ± 0.82 mm and 3.25 ± 0.82 mm laterally, 12.75 ± 0.42 mm and 13.00 ± 0.71 mm posterior to the midpoint of the anterior commissure-posterior commissure (AC-PC) line, and 1.83 ± 0.68 mm and 1.17 ± 0.75 mm inferior to the AC-PC line in the left and right LHb, respectively. The "Ring" angles (relative to the AC-PC level on the sagittal section plane) of the trajectories to the left and right LHb were 51.87° ± 6.67° and 52.00° ± 7.18°, respectively. The "Arc" angles (relative to the midline of the sagittal plane) were 33.82° ± 3.39° and 33.55° ± 3.72°, respectively. Moreover, there was small deviation of actual from planned target coordinates. No patient had surgery-, disease- or device-related adverse events during the perioperative period. Conclusion: Our results suggested that LHb-DBS surgery via frontal trajectory is safe, accurate, and feasible. This is an applicable work to report in detail the target coordinates and surgical path of human LHb-DBS. It has of great clinical reference value to treat more cases of LHb-DBS for TRD.

Progress in the development of a fully implantable brain-computer interface: the potential of sensing-enabled neurostimulators.

This perspective article investigates the performance of using a sensing-enabled neurostimulator as a motor brain-computer interface.

Probiotic Properties of a Spaceflight-induced Mutant Lactobacillus Plant- arum SS18-50 in Mice.

BACKGROUND: Probiotics are a group of bacteria that play a critical role in intestinal microbiota homeostasis and may help adjunctively treat certain diseases like metabolic and immune disorders. OBJECTIVE: We recently generated a space-flight mutated Lactobacillus plantarum SS18-50 with good in vitro probiotic characteristics. In the current research, we designed two in vivo experiments to evaluate whether L. plantarum SS18-50 had the ability to increase beneficial gut bacteria, regulate oxidative status and ameliorate inflammation in mice. METHODS: Experiments I: the ICR mice were gavaged with L. plantarum SS18-50 or its wild type L. plantarum GS18 at 107 or 109 CFU/kg BW daily for one month, during which the body weight was recorded weekly. The feces were collected to determine the abundance of two main beneficial bacterial groups including Lactobacillus and Bifidobacterium by selective culturing, while the total triglycerides and cholesterols in sera were determined using commercial kits. Experiment II: the mice were gavaged with loperamide hydrochloride (Lop) to develop oxidative stress and inflammation phenotypes. At the same time, the experimental mice were gavaged with L. plantarum SS18-50 or wild type L. plantarum GS18 at 107 or 109 CFU/kg BW daily for one month. At the end of the experiment, oxidative indicators (SOD and MDA) and inflammatory cytokines (IL-17A and IL-10) were measured by commercial kits. RESULTS: Results showed that L. plantarum SS18-50 increased the abundance of Lactobacillus and Bifidobacterium in mice after one month's administration. L. plantarum SS18-50 also showed the anti-oxidant activity by increasing SOD and decreasing MDA and exerted the anti-inflammatory effect by increasing IL-10 and decreasing IL-17A in Lop treated mice. Both the wild type stain and the space mutant had such biomedical effects, but L. plantarum SS18-50 was better in increasing gut beneficial bacteria and oxidative regulation than the wild type (P<0.05). CONCLUSION: We conclude that L. plantarum SS18-50 has a great potential to serve as a dietary functional probiotic supplement and/or adjunctive treatment strategy.

Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic Behaviors in Ten Pediatric Patients With Drug Resistant Epilepsy: An Observational Study.

Vagus nerve stimulation (VNS) is a safe and effective therapy for pediatric patients with drug-resistant epilepsy (DRE). However, in children with DRE, the effects of VNS on autistic behaviors remain controversial. We retrospectively collected data from 10 children with DRE who underwent VNS implantation and regular parameter regulation in three pediatric epilepsy centers, and completed the behavioral assessments, including the autistic behavior checklist and the child behavior checklist, at follow-ups 1 (mean 2.16 years) and 2 (mean 2.98 years). The 10 children maintained stable seizure control between the two follow-ups. Their autistic behaviors, especially in language, social and self-help, were reduced at follow-up 2 compared to follow-up 1 (p = 0.01, p = 0.01, respectively). Moreover, these improvements were not associated with their seizure control, whether it was positive or negative. These results suggested that the VNS had a positive effect on autistic behaviors, which provided a preliminary clinical basis that VNS may benefit to younger children with DRE comorbidity autism spectrum disorder (ASD).

A prediction model integrating synchronization biomarkers and clinical features to identify responders to vagus nerve stimulation among pediatric patients with drug-resistant epilepsy.

AIMS: Vagus nerve stimulation (VNS) is a neuromodulation therapy for children with drug-resistant epilepsy (DRE). The efficacy of VNS is heterogeneous. A prediction model is needed to predict the efficacy before implantation. METHODS: We collected data from children with DRE who underwent VNS implantation and received regular programming for at least 1 year. Preoperative clinical information and scalp video electroencephalography (EEG) were available in 88 children. Synchronization features, including phase lag index (PLI), weighted phase lag index (wPLI), and phase-locking value (PLV), were compared between responders and non-responders. We further adapted a support vector machine (SVM) classifier selected from 25 clinical and 18 synchronization features to build a prediction model for efficacy in a discovery cohort (n = 70) and was tested in an independent validation cohort (n = 18). RESULTS: In the discovery cohort, the average interictal awake PLI in the high beta band was significantly higher in responders than non-responders (p < 0.05). The SVM classifier generated from integrating both clinical and synchronization features had the best prediction efficacy, demonstrating an accuracy of 75.7%, precision of 80.8% and area under the receiver operating characteristic (AUC) of 0.766 on 10-fold cross-validation. In the validation cohort, the prediction model demonstrated an accuracy of 61.1%. CONCLUSION: This study established the first prediction model integrating clinical and baseline synchronization features for preoperative VNS responder screening among children with DRE. With further optimization of the model, we hope to provide an effective and convenient method for identifying responders before VNS implantation.

A novel uni-acupoint electroacupuncture stimulation method for pain relief.

Electroacupuncture stimulation (EAS) has been demonstrated effective for pain relief and treating other various diseases. However, the conventional way of EAS, the bi-acupoint method, is not suitable for basis study of acupoint specificity. Moreover, its operations are inconvenient and difficult to be persevered, especially for long-term, continuous and even imperative treatments. These disadvantages motivate designs of new EAS methods. We present a novel uni-acupoint electrical stimulation method, which is applied at a single acupoint and quite meets the needs of basis study and simpler clinical application. Its pain relief effect has been evaluated by animal tests of Wistar rats. During the experiments, rats were given 30 min 2/100 Hz uni- and bi-acupoint EAS and their nociceptive thresholds before and after EAS were attained by hot-plate test. The analgesic effect was defined as the change of nociceptive threshold and used to evaluate the effectiveness of uni-acupoint EAS for pain relief. The hot-plate test results indicated that analgesic effect of uni-acupoint group was significantly higher than that of the control group and there was no significant difference of analgesic effects between uni- and bi-acupoint EAS. The results suggested that uni-acupoint method was an effective EAS method and had comparable pain relief effect with bi-acupoint method.

Cause of Subharmonics in Local Field Potentials Recorded by Sensing-Enabled Neurostimulator.

Sensing-enabled neurostimulators have become an essential technology for recording local field potentials (LFPs) during neurostimulation. However, subharmonics from indeterminate sources make interpreting LFP recordings a challenge. In this study, we investigated the characteristics and the cause of the subharmonics recorded by sensing-enabled neurostimulators. We found that the amplitudes and frequencies of the subharmonics in clinical LFPs varied with stimulation parameters. Using simulated solutions, we demonstrated that these subharmonics were device-generated noise. The cause of the subharmonics was the ripples in the stimulation pulses residual in the final LFP recordings. Our results provided a method to discriminate the subharmonic artifacts and suggested that interpretation of the subharmonics at a fractional frequency of stimulations in LFP recordings should be performed carefully.Clinical Relevance- This study reveals the cause of subharmonics in LFP recordings for clinical neuroscience research.